The Therapy of Tacrolimus Combined With Entecavir on HBV Associated Glomerulonephritis : A Multicenter, Prospective, Randomized, Controlled, Single-blind Trial.
试验速览
- 阶段
- 4 期
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Remission rate of proteinuria
研究概览
简要总结
This study was to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis in china. Tacrolimus combined with entecavir rapidly and effectively induced remission of HBV-GN in Chinese adults. Meanwhile, Tacrolimus may have a synergistic antiviral effect with entecavir. The study protocol was reviewed and approved by Guangdong General Hospital's Ethic Committee, and all participants provided written informed consents. The study will be a prospective, randomized,controlled,single-blind, multi-centre, withdrawal study conducted by Guangdong general hospital, Guangdong Academy of Medical Sciences.there will be two phases, phase 1, Screening and enrolling 112 HBV-GN patients about one year,and phase 2, ongoing follow-up for 24 weeks.The data of all patients will be recorded in the HBV-GN electronic database.Before the randomisation, All patients will receive entecavir routine antiviral therapy for two weeks.And then they will be randomized to two different group,the treatment group: Tacrolimus combined with entecavir antiviral therapy,the control group: The Tacrolimus placebo and entecavir antiviral therapy. The Tacrolimus target trough concentration was 5-10 ng/mL during the therapy. The primary outcome variables were the number of patients who reached complete or partial remission (CR or PR) after the 25 week-treatment. CR was defined as <0.3 g/24 h proteinuria (UPCR<300mg/g.cr) or lower plus stable renal function (eGFR>50 ml/min/1.73 m2) and PR as proteinuria 0.3-3.0 g/24 h (UPCR 300-3000mg/g.cr) and 50% lower than baseline proteinuria plus stable renal function. Secondary outcome variables: 1) The number of patients who reached complete or partial remission (CR or PR) after the 13 week-treatment. 2) Serum creatinine (SCr) increased 2 times the baseline levels or 50% lower than the baseline eGFR(according to chronic kidney disease-EPI (CKD-EPI) )after the 25 week-treatment. 3)Serum HBV DNA was undetectable(HBV DNA<500copies/ml) at the end of 25 week-treatment. 4) The number of patients who present acute kidney injury at the end of 25 week-treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients aged between 18 and 65 years with HBV-GN;
- •All HBV-GN cases with biopsy-proven;
- •Evidence of chronic HBV infection based on the presence of HBsAg, HBeAg or HBV DNA in the serum;(HBsAg, HBeAg was positive, HBV DNA ≥10*3 IU/ml). Chronic HBV infection lasted for six months, and all patients did not receive the antiviral therapy in the past six months;
- •Proteinuria more than 3.0g/24h, UPCR>3000mg/g.cr, the result will be proofed by at least two tests;
- •No glucocorticoid and immunosuppressive treatment within the previous 2 weeks.
排除标准
- •The diagnosis of idiopathic membranous nephropathy(MN), systemic lupus erythematosus, malignancy, diabetes mellitus, severe infections or any other systemic disease known to be associated with secondary MN;
- •eGFR<30ml/min.1.73m*2;
- •Renal pathology showed that Tubular atrophy or Interstitial fibrosis was more than 50%;
- •The participant is allergy to tacrolimus, entecavir;
- •History of diabetes mellitus;
- •History of severe heart disease or cerebrovascular diseases;
- •Other active infection such as cytomegalovirus (CMV),Tuberculosis,Hepatitis A virus (HAV),Hepatitis C virus (HCV),Hepatitis D virus (HDV); Innate or acquired immunodeficiency; liver cirrhosis, liver malignment tumor;
- •Pregnant, trying to become pregnant or breast feeding;
研究组 & 干预措施
Tacrolimus & entecavir
Tacrolimus capsule, 0.5mg/capsule,1.0mg/capsule, 0.05-0.1mg/kg.d by mouth , every 12 hours for a day.Entecavir 0.5mg tablet by mouth every night.
干预措施: Tacrolimus &entecavir (Drug)
placebo & entecavir
Tacrolimus capsule, 0.5mg/capsule,1.0mg/capsule, 0.05-0.1mg/kg.d by mouth , every 12 hours for a day.Entecavir 0.5mg tablet by mouth every night.
干预措施: placebo & entecavir (Drug)
结局指标
主要结局
Remission rate of proteinuria
时间窗: 25 weeks
the number of patients who reached complete or partial remission (CR or PR) after the 25 week-treatment. CR was defined as \<0.3 g/24 h proteinuria (UPCR\<300mg/g.cr) or lower plus stable renal function (eGFR\>50 ml/min/1.73 m2) and PR as proteinuria 0.3-3.0 g/24 h (UPCR 300-3000mg/g.cr) and 50% lower than baseline proteinuria plus stable renal function.
次要结局
- Serum HBV DNA(25 weeks)
- Remission rate of proteinuria(13 weeks)
- The change of Scr(25 weeks)
- The rate of acute kidney injury(25 weeks)